Dennis C. J. J. Bergmans

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies

BACKGROUND Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING None.

Cross-colonisation with Pseudomonas aeruginosa of patients in an intensive care unit

BACKGROUND Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is usually preceded by colonisation of the respiratory tract. During outbreaks, colonisation with P aeruginosa is mainly derived from exogenous sources. The relative importance of different pathways of colonisation of P aeruginosa has rarely been determined in non-epidemic settings. METHODS In order to determine the importance of exogenous colonisation, all isolates of P aeruginosa obtained by surveillance and clinical cultures from two identical intensive care units (ICUs) were genotyped with pulsed field gel electrophoresis. RESULTS A total of 100 patients were studied, 44 in ICU 1 and 56 in ICU 2. Twenty three patients were colonised with P aeruginosa, seven at the start of the study or on admission and 16 of the remaining 93 patients became colonised during the study. Eight patients developed VAP due to P aeruginosa. The incidence of respiratory tract colonisation and VAP with P aeruginosa in our ICU was similar to that before and after the study period, and therefore represents an endemic situation. Genotyping of 118 isolates yielded 11 strain types: eight in one patient each, two in three patients each, and one type in eight patients. Based on chronological evaluation and genotypical identity of isolates, eight cases of cross-colonisation were identified. Eight (50%) of 16 episodes of acquired colonisation and two (25%) of eight cases of VAP due to P aeruginosa seemed to be the result of cross-colonisation. CONCLUSIONS Even in non-epidemic settings cross-colonisation seems to play an important part in the epidemiology of colonisation and infection with P aeruginosa.

Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial

IMPORTANCE Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION trialregister.nlIdentifier: NTR1780.

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units

ObjectiveAlthough the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DesignBased on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. Data SourcePublished data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were

Clinical review: Post-extubation laryngeal edema and extubation failure in critically ill adult patients

351 per patient (

Analysis of volatile organic compounds in exhaled breath to diagnose ventilator-associated pneumonia

32 per patient per day). All other costs were derived from the hospital administrative database for all individual patients. Results of Base-Case AnalysisPrevention of VAP led to mean total costs of

Colonization with Pseudomonas aeruginosa in patients developing ventilator-associated pneumonia.

16,119 and

Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia.

18,268 for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. Results of Sensitivity AnalysisPrevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than

Value of phenotyping methods as an initial screening of Pseudomonas aeruginosa in epidemiologic studies.

2,500, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. ConclusionsThis study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.

Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review.

Laryngeal edema is a frequent complication of intubation. It often presents shortly after extubation as post-extubation stridor and results from damage to the mucosa of the larynx. Mucosal damage is caused by pressure and ischemia resulting in an inflammatory response. Laryngeal edema may compromise the airway necessitating reintubation. Several studies show that a positive cuff leak test combined with the presence of risk factors can identify patients with increased risk for laryngeal edema. Meta-analyses show that pre-emptive administration of a multiple-dose regimen of glucocorticosteroids can reduce the incidence of laryngeal edema and subsequent reintubation. If post-extubation edema occurs this may necessitate medical intervention. Parenteral administration of corticosteroids, epinephrine nebulization and inhalation of a helium/oxygen mixture are potentially effective, although this has not been confirmed by randomized controlled trials. The use of non-invasive positive pressure ventilation is not indicated since this will delay reintubation. Reintubation should be considered early after onset of laryngeal edema to adequately secure an airway. Reintubation leads to increased cost, morbidity and mortality.